November 23, 2011 - Recognizing the great potential of gene therapy for saving and restoring vision, the Foundation Fighting Blindness is investing an unprecedented $8.25 million for six new gene therapy research projects, all of which are targeted to have treatments ready for clinical trials within three years. These grants are allocated through the Foundation's Translational Research Acceleration Program, which funds research projects with strong, near-term clinical potential.
This focused drive to advance gene therapy will include funding potential treatments for: choroideremia, X-linked retinoschisis, retinitis pigmentosa (GUCYD2 mutations), two forms of Leber congenital amaurosis (GUCYD2 and RPGRIP1 mutations) and a nanoparticle gene delivery system that's useful for treating diseases caused by larger genes.
It was just three years ago that the Foundation Fighting Blindness reported outstanding results from its first gene therapy clinical trials: Young adults with virtually no vision could, for the first time, read several lines on an eye chart and navigate in dimly lit settings. Since then, more than 40 patients taking part in gene therapy clinical trials to treat a form of Leber congenital amaurosis (LCA) have benefited from this remarkable emerging treatment.
The success of those first LCA studies set the stage for rapid expansion in gene therapy development. In fact, by the end of this year, there will be human studies of gene therapies underway for as many as five retinal diseases, including the aforementioned LCA, wet age-related macular degeneration (AMD), Stargardt disease, Usher syndrome type 1B and autosomal recessive retinitis pigmentosa caused by mutations in the MERTK gene. These studies are independent of the six newly funded projects.
Virtually all of the Foundation's gene therapy work to date has focused on correcting specific genetic defects — replacing bad genes with healthy genes — that cause particular diseases. Through this new investment, some researchers are seeking less restrictive approaches to gene therapy that may apply to more than one disease.
"Gene therapy can do much more than we originally envisioned. We are now seeing it used to deliver vision-saving proteins, stop the growth of unhealthy blood vessels in wet AMD and even harness retinal cells other than photoreceptors for vision," says the Foundation's chief research officer, Dr. Stephen Rose. "These disease-independent initiatives have become an important part of our portfolio, because they can apply to people regardless of their defective gene."
For example, the Foundation is funding a collaboration of The Institut de la Vision in Paris and the Friedrich Miescher Institute in Basel, Switzerland, which is developing a gene therapy to resurrect and reactivate cone cells that are compromised by a wide range of diseases.
In many inherited retinal conditions, including retinitis pigmentosa, cones stop working before they completely degenerate. The research team's gene therapy revives degenerating cones, enabling them to regain their ability to respond to light and provide vision. The treatment also improves the health of cones and extends their lifespan significantly. Because cones provide central, daytime and detailed vision — enabling someone to drive, read or see the faces of loved ones — having the ability to resurrect them could mean a lot to someone who has a retinal disease.
With an increased investment in disease-independent treatments, like this one, coupled with numerous gene replacement therapies for specific diseases, the Foundation is building a strong gene therapy portfolio that may benefit people affected by a range of conditions.
